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Muscular dystrophy

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Muscular dystrophy

Muscular Dystrophy
Classification and external resources
In affected muscle (right) the tissue becomes disorganized and the concentration of dystrophin (green) is greatly reduced, compared to normal muscle (left).
ICD-10 G71.0
ICD-9 359.0-359.1
MedlinePlus 001190
eMedicine orthoped/418
MeSH D009136

Muscular dystrophy (MD) is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion.[1][2] Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.[3]

In the 1860s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of thirteen boys with the most common and severe form of the disease, which now carries his name—Duchenne muscular dystrophy.

It soon became evident that the disease had more than one form. The other major forms are Becker, limb-girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss muscular dystrophy.[4] Duchenne and Becker muscular dystrophies, being caused by a mutation of a gene located on the X chromosome, predominantly affect males, although females can sometimes have severe symptoms as well. Most types of MD are multi-system disorders with manifestations in body systems including the heart, gastrointestinal system, nervous system, endocrine glands, eyes and brain.[4]

Apart from the nine major types of muscular dystrophy listed above, several MD-like conditions have also been identified. Normal intellectual, muscular, behavioral, bowel and sexual function is noticed in individuals with other forms of MD and MD-like conditions.[5][6] MD-affected individuals with susceptible intellectual impairment are diagnosed through molecular characteristics but not through problems associated with disability.[7] However, a third of patients who are severely affected with DMD may have cognitive impairment, behavioral, vision and speech problems.[8][9]

Signs and symptoms


These conditions are generally inherited, and the different muscular dystrophies follow various inheritance patterns. However, mutations of the dystrophin gene and nutritional defects (with no genetics history) at the prenatal stage are also possible in about 33% of people affected by DMD.[11] The main cause of the Duchenne and Becker types of muscular dystrophy is the muscle tissue's cytoskeletal impairment to properly create the functional protein dystrophin and dystrophin-associated protein complex.

Dystrophin protein is found in muscle fibre membrane; its helical nature allows it to act like a spring or shock absorber. Dystrophin links actin (cytoskeleton) and dystroglycans of the muscle cell plasma membrane, known as the sarcolemma (extracellular). In addition to mechanical stabilization, dystrophin also regulates calcium levels.. Recent studies on the interaction of proteins with missense mutations and its neighbors showed high degree of rigidity associated with central hub proteins involved in protein binding and flexible subnetworks having molecular functions involved with calcium.[12]


Histopathology of gastrocnemius muscle from patient who died of pseudohypertrophic muscular dystrophy, Duchenne type. Cross section of muscle shows extensive replacement of muscle fibers by adipose cells.

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase (CpK3), electromyography, electrocardiography and DNA analysis.

A physical examination and the patient's medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.

Often, there is a loss of muscle mass (wasting), which may be hard to see because some types of muscular dystrophy cause a buildup of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.


There is no known cure for muscular dystrophy, although significant headway is being made with antisense oligonucleotides.[13] Physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis), speech therapy and orthopedic instruments (e.g., wheelchairs, standing frames and powered mobile arm supports) may be helpful. Inactivity (such as bed rest, sitting for long periods) and bodybuilding efforts to increase myofibrillar hypertrophy can worsen the disease.

There is no specific treatment for any of the forms of muscular dystrophy. Physiotherapy, aerobic exercise, low intensity anabolic steroids, prednisone supplements may help to prevent contractures and maintain muscle tone. Orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine, phenytoin, or mexiletine, but no actual long term treatment has been found.

Occupational therapy assists the individual with MD to engage in activities of daily living (such as self-feeding and self-care activities) and leisure activities at the most independent level possible. This may be achieved with use of adaptive equipment or the use of energy conservation techniques. Occupational therapy may implement changes to a person's environment, both at home or work, to increase the individual's function and accessibility. Occupational therapists also address psychosocial changes and cognitive decline which may accompany MD, as well as provide support and education about the disease to the family and individual.[14]

High dietary intake of lean meat, seafood, pulses, olive oil, antioxidants such as leafy vegetables and bell peppers, and fruits like blueberry and cherry is advised. Decreased intake of refined food, trans fats, and caffeinated and alcoholic beverages is also advised, as is a check for any food allergies.[15]

After diagnosis, medical care may include services in neurology, nutrition, gastroenterology, respiratory care, cardiac care, orthopedics, psychosocial, rehabilitation, and oral care.


Prognosis depends on the individual form of muscular dystrophy. In some cases a person with a muscle disease will get progressively weaker to the extent that it shortens life span due to heart and breathing complications. However, some of the muscle diseases do not affect life expectancy at all. There is a tremendous amount of ongoing research to find cures and treatments to slow muscle weakness. There is also a lot of research to learn how best to manage the breathing and heart issues which generally impact lifespan more than the muscle weakness.


Type OMIM Gene Description
Becker muscular dystrophy 300376 DMD Becker muscular dystrophy (BMD) is a less severe variant of Duchenne muscular dystrophy and is caused by the production of a truncated, but partially functional form of dystrophin.[4] Survival is usually into old age.[16] Affects only boys (with extremely rare exceptions)
Congenital muscular dystrophy Multiple Multiple Age at onset: birth; symptoms include general muscle weakness and possible joint deformities; disease progresses slowly; shortened life span.[17]

Congenital muscular dystrophy includes several disorders with a range of symptoms. Muscle degeneration may be mild or severe. Problems may be restricted to skeletal muscle, or muscle degeneration may be paired with effects on the brain and other organ systems. A number of the forms of the congenital muscular dystrophies are caused by defects in proteins that are thought to have some relationship to the dystrophin-glycoprotein complex and to the connections between muscle cells and their surrounding cellular structure. Some forms of congenital muscular dystrophy show severe brain malformations, such as lissencephaly and hydrocephalus.[4]

Duchenne muscular dystrophy 310200 DMD Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy; it generally affects only boys (with extremely rare exceptions), becoming clinically evident when a child begins walking. By age 10, the child may need braces for walking and by age 12, most patients are unable to walk.[18] Life span ranges from 15 to 51.[18] In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. The amount of dystrophin correlates with the severity of the disease (i.e., the less dystrophin present, the more severe the phenotype). Since the gene is on the X chromosome, this disorder affects primarily males, and females who are carriers have milder symptoms. Sporadic mutations in this gene occur frequently, accounting for a third of cases. The remaining two-thirds of cases are inherited in a recessive pattern.

Dystrophin is part of a complex structure involving several other protein components. The "dystrophin-glycoprotein complex" helps anchor the structural skeleton (cytoskeleton) within the muscle cells, through the outer membrane (sarcolemma) of each cell, to the tissue framework (extracellular matrix) that surrounds each cell. Due to defects in this assembly, contraction of the muscle leads to disruption of the outer membrane of the muscle cells and eventual weakening and wasting of the muscle.[4]

Distal muscular dystrophy 254130 DYSF Distal muscular dystrophies' age at onset: 20 to 60 years; symptoms include weakness and wasting of muscles of the hands, forearms, and lower legs; progress is slow and not life-threatening.[16]

Miyoshi myopathy, one of the distal muscular dystrophies, causes initial weakness in the calf muscles, and is caused by defects in the same gene responsible for one form of LGMD (Limb Girdle Muscular Dystrophy).[4]

Emery-Dreifuss muscular dystrophy 310300, 181350 EMD, LMNA Emery-Dreifuss Muscular Dystrophy patients normally present in childhood and the early teenage years with contractures. Clinical signs include muscle weakness and wasting, starting in the distal limb muscles and progressing to involve the limb-girdle muscles. Most patients also suffer from cardiac conduction defects and arrhythmias which, if left untreated, increase the risk of stroke and sudden death.

There are three subtypes of Emery-Dreifuss Muscular Dystrophy, distinguishable by their pattern of inheritance: X-Linked, autosomal dominant and autosomal recessive. The X-linked form is the most common. Each type varies in prevalence and symptoms. The disease is caused by mutations in the LMNA gene, or more commonly, the EMD gene. Both genes encode for protein componenets of the nuclear envelope. However, how these mutations cause the pathogenesis is not well understood.[19]

Facioscapulohumeral muscular dystrophy 158900 DUX4 Facioscapulohumeral muscular dystrophy (FSHD) initially affects the muscles of the face, shoulders, and upper arms with progressive weakness. Symptoms usually develop in the teenage years. Some affected individuals become severely disabled. The pattern of inheritance is autosomal dominant, but there are a significant number of spontaneous mutations. Seminal research published in August 2010 documents that two defects are needed for FSHD, which for the first time provides a unifying theory for the underlying genetics of FSHD. The first is the deletion of D4Z4 repeats and the second is a "toxic gain of function" of the DUX4 gene.[4][20]


Facioscapulohumeral muscular dystrophy (FSHD) occurs both in males and females.

Limb-girdle muscular dystrophy Multiple Multiple Limb-girdle muscular dystrophy is also called LGMD. Affects both boys and girls. LGMDs all show a similar distribution of muscle weakness, affecting both upper arms and legs. Many forms of LGMD have been identified, showing different patterns of inheritance (autosomal recessive vs. autosomal dominant). In an autosomal recessive pattern of inheritance, an individual receives two copies of the defective gene, one from each parent. The recessive LGMDs are more frequent than the dominant forms, and usually have childhood or teenage onset. The dominant LGMDs usually show adult onset. Some of the recessive forms have been associated with defects in proteins that make up the dystrophin-glycoprotein complex.[4] Though a person normally leads a normal life with some assistance, in some extreme cases, death from LGMD occurs due to cardiopulmonary complications.[22]
Myotonic muscular dystrophy 160900, 602668 DMPK, ZNF9 Myotonic muscular dystrophy is an autosomal dominant condition that presents with myotonia (delayed relaxation of muscles) as well as muscle wasting and weakness.[23] Myotonic dystrophy varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, eyes, and gastrointestinal tract.

Myotonic muscular dystrophy type 1 (DM1), also known as Steinert disease, is the most common adult form of muscular dystrophy. It results from the expansion of a short (CTG) repeat in the DNA sequence of the DMPK (myotonic dystrophy protein kinase) gene. Myotonic muscular dystrophy type 2 (DM2) is much rarer and is a result of the expansion of the CCTG repeat in the ZNF9 (zinc finger protein 9) gene. While the exact mechanisms of action are not known, these molecular changes may interfere with the production of important muscle proteins.[4]

Oculopharyngeal muscular dystrophy 164300 PABPN1 Oculopharyngeal MD's age at onset: 40 to 70 years; symptoms affect muscles of eyelids, face, and throat followed by pelvic and shoulder muscle weakness, has been attributed to a short repeat expansion in the genome which regulates the translation of some genes into functional proteins.[4]

Research funding

Within the United States, the three primary federally funded organizations that focus on muscular dystrophy research, including gene therapy, regenerative medicine) etc., include the National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Institute of Child Health and Human Development (NICHD).[4]

In 1966, the Muscular Dystrophy Association began its annual Jerry Lewis MDA Telethon, which has probably done more to raise awareness of muscular dystrophy than any other event or initiative. Disability rights advocates, however, have criticized the Jerry Lewis Telethon for portraying victims of the disease as deserving pity rather than respect.[24]

On December 18, 2001, the MD CARE Act was signed into law and amends the Public Health Service Act to provide research for the various muscular dystrophies. This law also established the Muscular Dystrophy Coordinating Committee to help focus research efforts through a coherent research strategy.[25][26]

See also


  1. ^ R H Brown Jr., J R Mendell (2005). Harrison's Principles of Internal Medicine. p. 2527.  
  2. ^ Muscular Dystrophy Campaign Retrieved 9 April 2007.
  3. ^ Emery AE (2002). "The muscular dystrophies". Lancet 359 (9307): 687–695.  
  4. ^ a b c d e f g h i j k May 2006 report to Congress on Implementation of the MD CARE Act, as submitted by Department of Health and Human Service's National Institutes of Health
  5. ^
  6. ^
  7. ^
  8. ^
  9. ^
  10. ^
  11. ^ Motlagh B, MacDonald JR, Tarnoplosky MA. Nutritional inadequacy in adults with muscular dystrophy. Muscle Nerve. 2005;31(6):713-8.
  12. ^ Sharma, Ankush; Ferraro MV; Maiorano F; Blanco FDV; Guarracino MR (February 2014). "Rigidity and flexibility in protein-protein interaction networks: a case study on neuromuscular disorders".  
  13. ^
  14. ^ R.M. Lehman & G.L. McCormack, 2001. Neurogenic and Myopathic Dysfunction pp. 802-803. In L. Pedretti and M Early Occupational Therapy Skills for Physical Dysfunction 5th ED St Louis MO: Mosby
  15. ^
  16. ^ a b [1]: MD USA Website (accessed 03SEP2007)
  17. ^ "Congenital Muscular Dystrophy (CMD)". MDA. Retrieved 27 April 2012. 
  18. ^ a b
  19. ^ Emedicine re EDMD Retrieved 30 July 2007.
  20. ^ Kolata, Gina (19 August 2010). "Reanimated 'Junk' DNA Is Found to Cause Disease".  
  21. ^ Lemmers, Richard; Patrick J. van der Vliet, Rinse Klooster, Sabrina Sacconi, Pilar Camaño, Johannes G. Dauwerse, Lauren Snider, Kirsten R. Straasheijm, Gert Jan van Ommen, George W. Padberg, Daniel G. Miller, Stephen J. Tapscott, Rabi Tawil, Rune R. Frants, and Silvère M. van der Maarel (19 August 2010). "A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy". Science 329 (5999): 1650–3.  
  22. ^ Jenkins, Simon P.R. (2005). Sports Science Handbook:I - Z. Brentwood, Essex: Multi-Science Publ. Co. p. 121.  
  23. ^ Turner, C; Hilton-Jones D. (2010). "The myotonic dystrophies: diagnosis and management". J Neurol Neurosurg Psychiatry 81: 358–367.  
  24. ^ Jon Wiener, "The End of the Jerry Lewis Telethon--It's About Time.", Sept. 2, 2011.
  25. ^ H.R. 717--107th Congress (2001): MD-CARE Act, (database of federal legislation), (accessed Jul 29, 2007)
  26. ^ Public Law 107-84, PDF as retrieved from NIH website

External links

  • Muscular dystrophies at DMOZ
  • National Registry for Myotonic Dystrophy and FSHD
  • FSH Society for Fascioscapulohumeral muscular dystrophy (USA and Worldwide)
  • FSHD Canada Foundation (CAN)
  • FSHD Europe (EU)
  • FSHD Global Research Foundation (Australia)
  • FSHD Stichting (Netherlands)
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